Translational Control in the Latency of Apicomplexan Parasites

Michael J. Holmes, Leonardo da Silva Augusto, Min Zhang, Ronald C. Wek, William J. Sullivan

Research output: Contribution to journalReview article

17 Scopus citations

Abstract

Apicomplexan parasites Toxoplasma gondii and Plasmodium spp. use latent stages to persist in the host, facilitate transmission, and thwart treatment of infected patients. Therefore, it is important to understand the processes driving parasite differentiation to and from quiescent stages. Here, we discuss how a family of protein kinases that phosphorylate the eukaryotic initiation factor-2 (eIF2) function in translational control and drive differentiation. This translational control culminates in reprogramming of the transcriptome to facilitate parasite transition towards latency. We also discuss how eIF2 phosphorylation contributes to the maintenance of latency and provides a crucial role in the timing of reactivation of latent parasites towards proliferative stages. Latent stages are critical to both pathogenesis and transmission of apicomplexan parasites. Differentiation into a latent stage can be induced by stress, which is sensed by eIF2 kinases that initiate the integrated stress response. The integrated stress response causes a decrease in general protein synthesis that diverts energy into the preferential translation of certain mRNAs likely to drive progression to latency. Translational control helps to maintain parasite latency until transmission, after which the process is reversed and proliferation resumes.

Original languageEnglish (US)
Pages (from-to)947-960
Number of pages14
JournalTrends in Parasitology
Volume33
Issue number12
DOIs
StatePublished - Dec 2017

Keywords

  • Plasmodium
  • Toxoplasma
  • eIF2
  • latency
  • translational control

ASJC Scopus subject areas

  • Parasitology
  • Infectious Diseases

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